BR112020009290A2 - derivados de pirimidina para a prevenção e tratamento de infecções bacterianas - Google Patents
derivados de pirimidina para a prevenção e tratamento de infecções bacterianas Download PDFInfo
- Publication number
- BR112020009290A2 BR112020009290A2 BR112020009290-8A BR112020009290A BR112020009290A2 BR 112020009290 A2 BR112020009290 A2 BR 112020009290A2 BR 112020009290 A BR112020009290 A BR 112020009290A BR 112020009290 A2 BR112020009290 A2 BR 112020009290A2
- Authority
- BR
- Brazil
- Prior art keywords
- amine
- cyclopropyl
- purin
- difluorphenyl
- propylthio
- Prior art date
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- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 139
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title claims abstract description 76
- 208000035143 Bacterial infection Diseases 0.000 title claims abstract description 44
- 208000022362 bacterial infectious disease Diseases 0.000 title claims abstract description 43
- 230000002265 prevention Effects 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 36
- 230000032770 biofilm formation Effects 0.000 claims abstract description 23
- 239000012620 biological material Substances 0.000 claims abstract description 21
- 241000124008 Mammalia Species 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 238000003745 diagnosis Methods 0.000 claims abstract description 9
- 238000004393 prognosis Methods 0.000 claims abstract description 7
- 210000003709 heart valve Anatomy 0.000 claims abstract description 5
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 124
- 150000003839 salts Chemical class 0.000 claims description 90
- -1 3,4-difluorphenyl Chemical group 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 74
- 230000015572 biosynthetic process Effects 0.000 claims description 50
- 208000015181 infectious disease Diseases 0.000 claims description 39
- 239000000651 prodrug Chemical class 0.000 claims description 39
- 229940002612 prodrug Drugs 0.000 claims description 39
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 34
- 229910052751 metal Inorganic materials 0.000 claims description 33
- 239000002184 metal Substances 0.000 claims description 33
- 230000001580 bacterial effect Effects 0.000 claims description 31
- 150000003863 ammonium salts Chemical class 0.000 claims description 28
- 239000007943 implant Substances 0.000 claims description 28
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 17
- MVHTVXFDPMHZNE-UHFFFAOYSA-N cyclopentane-1,2,3-triol Chemical compound OC1CCC(O)C1O MVHTVXFDPMHZNE-UHFFFAOYSA-N 0.000 claims description 17
- 241000191963 Staphylococcus epidermidis Species 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 238000011109 contamination Methods 0.000 claims description 13
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 12
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims description 10
- 229960003085 meticillin Drugs 0.000 claims description 10
- 241000295644 Staphylococcaceae Species 0.000 claims description 9
- 150000004820 halides Chemical class 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- 239000003550 marker Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 108010059993 Vancomycin Proteins 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 238000002513 implantation Methods 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000003568 thioethers Chemical group 0.000 claims description 8
- 229960003165 vancomycin Drugs 0.000 claims description 8
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims description 8
- MYPYJXKWCTUITO-LYRMYLQWSA-O vancomycin(1+) Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C([O-])=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)[NH2+]C)[C@H]1C[C@](C)([NH3+])[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-O 0.000 claims description 8
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 claims description 7
- 108010015899 Glycopeptides Proteins 0.000 claims description 7
- 102000002068 Glycopeptides Human genes 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- XXHGDLJQCZLECB-UHFFFAOYSA-N pyrimidin-4-amine;hydrochloride Chemical compound Cl.NC1=CC=NC=N1 XXHGDLJQCZLECB-UHFFFAOYSA-N 0.000 claims description 7
- KKFBLBNKBUCRQQ-MAUKXSAKSA-N 9-cyclopentyl-N-[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]-2-propylsulfanylpurin-6-amine Chemical compound C1(CCCC1)N1C2=NC(=NC(=C2N=C1)N[C@H]1[C@@H](C1)C1=CC(=C(C=C1)F)F)SCCC KKFBLBNKBUCRQQ-MAUKXSAKSA-N 0.000 claims description 6
- CRHBFQLTXJJELF-XJKSGUPXSA-N 9-cyclopropyl-N-[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]-2-propylsulfanylpurin-6-amine Chemical compound C1(CC1)N1C2=NC(=NC(=C2N=C1)N[C@H]1[C@@H](C1)C1=CC(=C(C=C1)F)F)SCCC CRHBFQLTXJJELF-XJKSGUPXSA-N 0.000 claims description 6
- LDHQGNDJYDKPNT-UONOGXRCSA-N 9-methyl-N-[(1R,2S)-2-phenylcyclopropyl]-2-propylsulfanylpurin-6-amine Chemical compound CN1C2=NC(=NC(=C2N=C1)N[C@H]1[C@@H](C1)C1=CC=CC=C1)SCCC LDHQGNDJYDKPNT-UONOGXRCSA-N 0.000 claims description 6
- 241000192125 Firmicutes Species 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- AOTWIFLKURJQGE-UHFFFAOYSA-N n-cyclopropylaniline Chemical compound C1CC1NC1=CC=CC=C1 AOTWIFLKURJQGE-UHFFFAOYSA-N 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
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- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 230000002147 killing effect Effects 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 3
- 150000002429 hydrazines Chemical class 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 241000193990 Streptococcus sp. 'group B' Species 0.000 claims description 2
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- 150000007530 organic bases Chemical class 0.000 claims description 2
- 125000000101 thioether group Chemical group 0.000 claims 3
- DUFGYCAXVIUXIP-UHFFFAOYSA-N 4,6-dihydroxypyrimidine Chemical class OC1=CC(O)=NC=N1 DUFGYCAXVIUXIP-UHFFFAOYSA-N 0.000 claims 2
- 230000029936 alkylation Effects 0.000 claims 2
- 238000005804 alkylation reaction Methods 0.000 claims 2
- 125000001033 ether group Chemical group 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- YFYYRKDBDBILSD-UHFFFAOYSA-N 6-amino-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1 YFYYRKDBDBILSD-UHFFFAOYSA-N 0.000 claims 1
- 101100509468 Arabidopsis thaliana JASON gene Proteins 0.000 claims 1
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- RHZLYSSPVRJLMD-UHFFFAOYSA-N N-(2-phenylcyclopropyl)-7H-purin-6-amine Chemical compound C1C(NC=2C=3NC=NC=3N=CN=2)C1C1=CC=CC=C1 RHZLYSSPVRJLMD-UHFFFAOYSA-N 0.000 claims 1
- IZUCQZDGINQAGV-SMDDNHRTSA-N N-[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]-9-methyl-2-propylsulfanylpurin-6-amine Chemical group FC=1C=C(C=CC=1F)[C@H]1[C@@H](C1)NC1=C2N=CN(C2=NC(=N1)SCCC)C IZUCQZDGINQAGV-SMDDNHRTSA-N 0.000 claims 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
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- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
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- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Neurosurgery (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18156797.5A EP3527571A1 (en) | 2018-02-14 | 2018-02-14 | Pyrimidine derivatives for prevention and treatment of bacterial infection |
| EP18156797.5 | 2018-02-14 | ||
| PCT/EP2019/053711 WO2019158655A1 (en) | 2018-02-14 | 2019-02-14 | Pyrimidine derivatives for prevention and treatment of bacterial infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112020009290A2 true BR112020009290A2 (pt) | 2020-12-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112020009290-8A BR112020009290A2 (pt) | 2018-02-14 | 2019-02-14 | derivados de pirimidina para a prevenção e tratamento de infecções bacterianas |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US11434241B2 (zh) |
| EP (2) | EP3527571A1 (zh) |
| JP (1) | JP7316672B2 (zh) |
| CN (1) | CN111386271B (zh) |
| AU (1) | AU2019220404B2 (zh) |
| BR (1) | BR112020009290A2 (zh) |
| CA (1) | CA3090945A1 (zh) |
| DK (1) | DK3752506T3 (zh) |
| ES (1) | ES2939004T3 (zh) |
| WO (1) | WO2019158655A1 (zh) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3128304A1 (en) * | 2019-04-18 | 2020-10-22 | Universite De Liege | Pyrimidine derivatives for prevention and treatment of gram-negative bacterial infection, contamination and fouling |
| WO2021016263A1 (en) * | 2019-07-21 | 2021-01-28 | University Of Virginia Patent Foundation | Cysteine binding compositions and methods of use thereof |
| US20240139371A1 (en) | 2021-02-26 | 2024-05-02 | Université de Liège | New antimicrobial and antithrombogenic medical device |
| WO2023213198A1 (zh) * | 2022-05-04 | 2023-11-09 | 华东师范大学 | 芳香稠环化合物作为trek-1激活剂的用途、包含其的药物组合物、镇痛剂 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6717061A (zh) * | 1966-12-21 | 1968-06-24 | ||
| AR017014A1 (es) * | 1997-07-22 | 2001-08-22 | Astrazeneca Ab | Compuestos de triazolo [4,5-d]pirimidina, composiciones farmaceuticas, uso de los mismos para preparar medicamentos y procesos para la preparacionde dichos compuestos |
| TWI229674B (en) * | 1998-12-04 | 2005-03-21 | Astra Pharma Prod | Novel triazolo[4,5-d]pyrimidine compounds, pharmaceutical composition containing the same, their process for preparation and uses |
| JP2008516938A (ja) * | 2004-10-15 | 2008-05-22 | アストラゼネカ アクチボラグ | 置換アデニンとその使用 |
| WO2009034386A1 (en) * | 2007-09-13 | 2009-03-19 | Astrazeneca Ab | Derivatives of adenine and 8-aza-adenine and uses thereof-796 |
| EP3292867B1 (en) | 2016-09-09 | 2019-05-15 | Université de Liège | Triazolo(4,5-d)pyrimidine derivatives for use in the prevention and treatment of bacterial infection |
| US10905691B2 (en) * | 2016-09-09 | 2021-02-02 | Université de Liège | Use of triazolo(4,5-d)pyrimidine derivatives for prevention and treatment of bacterial infection |
| CA3128304A1 (en) * | 2019-04-18 | 2020-10-22 | Universite De Liege | Pyrimidine derivatives for prevention and treatment of gram-negative bacterial infection, contamination and fouling |
-
2018
- 2018-02-14 EP EP18156797.5A patent/EP3527571A1/en not_active Withdrawn
-
2019
- 2019-02-14 ES ES19708025T patent/ES2939004T3/es active Active
- 2019-02-14 BR BR112020009290-8A patent/BR112020009290A2/pt unknown
- 2019-02-14 WO PCT/EP2019/053711 patent/WO2019158655A1/en unknown
- 2019-02-14 US US16/958,023 patent/US11434241B2/en active Active
- 2019-02-14 EP EP19708025.2A patent/EP3752506B1/en active Active
- 2019-02-14 AU AU2019220404A patent/AU2019220404B2/en active Active
- 2019-02-14 CA CA3090945A patent/CA3090945A1/en active Pending
- 2019-02-14 JP JP2020540769A patent/JP7316672B2/ja active Active
- 2019-02-14 CN CN201980005921.8A patent/CN111386271B/zh active Active
- 2019-02-14 DK DK19708025.2T patent/DK3752506T3/da active
Also Published As
| Publication number | Publication date |
|---|---|
| JP7316672B2 (ja) | 2023-07-28 |
| US11434241B2 (en) | 2022-09-06 |
| CA3090945A1 (en) | 2019-08-22 |
| KR20200121322A (ko) | 2020-10-23 |
| ES2939004T3 (es) | 2023-04-18 |
| WO2019158655A1 (en) | 2019-08-22 |
| AU2019220404B2 (en) | 2023-07-13 |
| DK3752506T3 (da) | 2023-02-13 |
| CN111386271A (zh) | 2020-07-07 |
| EP3752506A1 (en) | 2020-12-23 |
| JP2021513511A (ja) | 2021-05-27 |
| CN111386271B (zh) | 2023-05-30 |
| AU2019220404A1 (en) | 2020-05-07 |
| US20210061804A1 (en) | 2021-03-04 |
| EP3752506B1 (en) | 2022-12-14 |
| EP3527571A1 (en) | 2019-08-21 |
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